We are studying a post-translation modification of tubulin involving the reversible enzymatic addition of a C-terminal tyrosine. We have studied whether tyrosylation alters affinity for other cell components with respect to binding of microtubule-associated proteins to microtubules, and of phospholipid vesicles to tubulin. The finding that subunits are preferred by the tyrosylating enzyme, and oligomers or polymers by the detyrosylating enzyme, raises the question of whether the modification is coupled to assembly. In this connection steady-state treadmilling rates have been compared. With respect to tubulin structure, we have found an approach toward characterizing that species which is not susceptible to the modification in vitro, and the fact that this species is modified in vivo has resolved a paradox relating to membrane-bound tubulin. The increased rate of tyrosylation we observed in chemotactically stimulated leukocytes suggests a relation to cytoskeletal rearrangement. Increased rates in leukocytes of patients with Chediak-Higashi disease offer a possible, if remote, chance to find the molecular basis of the disease.